The present invention relates to a process for preparing acylated amino esters and to a novel process for preparing optically active amino esters from racemic amino esters with a carboxylic ester as acylating agent, whose acid component has a halogen, nitrogen, oxygen or sulfur atom neighboring the carbonyl carbon atom, in the presence of a hydrolase selected from the group of amidase, protease, esterase and lipase, and subsequent separation of the enantioselectively acylated amino ester from the non-acylated other enantiomer of the amino ester.
Resolution of racemic primary and secondary amines by reaction with a carboxylic ester in the presence of a hydrolase is described in WO 95/08636 and WO 96/23894, and in a review article by Balkenhohl et al. in J. prakt. Chem. 339 (1997) 381-384. The preferred amines mentioned therein are primary arylalkylamines and heteroatom-substituted amines. However, no reference to the usability of amino esters is to be found in any of the three publications.
Gotor et al. (Tetrahedron: Asymmetry, 1997, 37-40) describe the enantioselective acylation of ethyl 3-aminobutyrate with ethyl acetate catalyzed by Candida antarctica Lipase (SP 435). However, the amounts of enzyme required for the catalysis are enormous (50% of the weight of the substrate), so that a process based on this is not economic. In addition, the enantioselectivity of the process is too low. It achieves selectivity only in the region of E=70-90.